The Chichibabin pyridine synthesis () is a method for synthesizing

pyridine Pyridine is a basic (chemistry), basic heterocyclic compound, heterocyclic organic compound with the chemical formula . It is structurally related to benzene, with one methine group replaced by a nitrogen atom . It is a highly flammable, weak ...

rings. The reaction involves the

condensation reaction In organic chemistry, a condensation reaction is a type of chemical reaction in which two molecules are combined to form a single molecule, usually with the loss of a small molecule such as water. If water is lost, the reaction is also known as a ...

aldehydes In organic chemistry, an aldehyde () (lat. ''al''cohol ''dehyd''rogenatum, dehydrogenated alcohol) is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred ...

ketones In organic chemistry, a ketone is an organic compound with the structure , where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group (a carbon-oxygen double bond C=O). The simplest ketone is acetone ( ...

α,β-unsaturated carbonyl compound α,β-Unsaturated carbonyl compounds are organic compounds with the general structure (O=CR)−Cα=Cβ−R. Such compounds include enones and enals, but also carboxylic acids and the corresponding esters and amides. In these compounds, the carb ...

s, or any combination of the above, with

ammonia Ammonia is an inorganic chemical compound of nitrogen and hydrogen with the chemical formula, formula . A Binary compounds of hydrogen, stable binary hydride and the simplest pnictogen hydride, ammonia is a colourless gas with a distinctive pu ...

. It was reported by

Aleksei Chichibabin Alekséy Yevgényevich Chichibábin (; – 15 August 1945) was a Soviet Union, Soviet Russian organic chemist. His name is also written ''Alexei Yevgenievich Chichibabin'' and ''Alexei Euguenievich Tchitchibabine''. Life Chichibábin was born ...

in 1924. Methyl-substituted pyridines, which show widespread uses among multiple fields of applied chemistry, are prepared by this methodology.

Representative syntheses

The syntheses are presently conduced commercially in the presence of oxide catalysts such as modified

alumina Aluminium oxide (or aluminium(III) oxide) is a chemical compound of aluminium and oxygen with the chemical formula . It is the most commonly occurring of several aluminium oxides, and specifically identified as aluminium oxide. It is commonly ...

(Al₂O₃) or

silica Silicon dioxide, also known as silica, is an oxide of silicon with the chemical formula , commonly found in nature as quartz. In many parts of the world, silica is the major constituent of sand. Silica is one of the most complex and abundant f ...

(SiO₂). The reactants are passed over the catalyst at 350–500 °C. 2-Methylpyridine- and

4-methylpyridine 4-Methylpyridine is the organic compound with the formula CH3C5H4N. It is one of the three isomers of methylpyridine. This pungent liquid is a building block for the synthesis of other heterocyclic compounds. Its conjugate acid, the 4-methylpyri ...

are produced as a mixture from acetaldehyde and ammonia. 3-Methylpyridine and pyridine are produced from

acrolein Acrolein (systematic name: propenal) is the simplest unsaturated aldehyde. It is a colorless liquid with a foul and acrid aroma. The smell of burnt fat (as when cooking oil is heated to its smoke point) is caused by glycerol in the burning fat ...

and ammonia. Acrolein and propionaldehyde react with ammonia affords mainly 3-methylpyridine. 5-Ethyl-2-methylpyridine is produced from

paraldehyde Paraldehyde is the cyclic trimer (chemistry), trimer of acetaldehyde molecules. Formally, it is a derivative of 1,3,5-trioxane, with a methyl group substituted for a hydrogen atom at each carbon. The corresponding tetramer is metaldehyde. A colo ...

and ammonia.

Mechanism and optimizations

These syntheses involve many reactions such as imine synthesis, base-catalyzed

aldol condensation An aldol condensation is a condensation reaction in organic chemistry in which two carbonyl moieties (of aldehydes or ketones) react to form a β-hydroxyaldehyde or β-hydroxyketone (an aldol reaction), and this is then followed by dehydration t ...

s, and

Michael reaction In organic chemistry, the Michael reaction or Michael 1,4 addition is a reaction between a Michael donor (an enolate or other nucleophile) and a Michael acceptor (usually an α,β-unsaturated carbonyl) to produce a Michael adduct by creating a c ...

Many efforts have been made to improve the method. Conducting the reaction in the gas phase in the presence of

aluminium(III) oxide Aluminium oxide (or aluminium(III) oxide) is a chemical compound of aluminium and oxygen with the chemical formula . It is the most commonly occurring of several aluminium oxides, and specifically identified as aluminium oxide. It is commonly c ...

zeolite Zeolites are a group of several microporous, crystalline aluminosilicate minerals commonly used as commercial adsorbents and catalysts. They mainly consist of silicon, aluminium, oxygen, and have the general formula ･y where is either a meta ...

(yield 98.9% at 500 K),

From nitriles

Of the many variations have been explored. one approach employs nitriles as the nitrogen source. For example,

acrylonitrile Acrylonitrile is an organic compound with the formula and the structure . It is a colorless, volatile liquid. It has a pungent odor of garlic or onions. Its molecular structure consists of a vinyl group () linked to a nitrile (). It is an im ...

and acetone affords 2-methylpyridine uncontaminated with the 4-methyl derivative. In another variation, alkynes and nitriles react in the presence of organocobalt catalysts, a reaction inspired by

alkyne trimerization An alkyne trimerisation is a +2+2nbsp; cycloaddition reaction in which three alkyne units () react to form a benzene ring. The reaction requires a metal catalyst. The process is of historic interest as well as being applicable to organic synthes ...

References

{{DEFAULTSORT:Chichibabin Pyridine Synthesis Pyridine forming reactions Heterocycle forming reactions Name reactions Soviet inventions

Representative syntheses

Mechanism and optimizations

From nitriles

See also

References